rs549507714
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
The NM_001018115.3(FANCD2):c.3494G>A(p.Arg1165Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000993 in 1,611,224 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1165W) has been classified as Uncertain significance.
Frequency
Consequence
NM_001018115.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FANCD2 | NM_001018115.3 | c.3494G>A | p.Arg1165Gln | missense_variant | 35/44 | ENST00000675286.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FANCD2 | ENST00000675286.1 | c.3494G>A | p.Arg1165Gln | missense_variant | 35/44 | NM_001018115.3 | P2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000159 AC: 40AN: 251454Hom.: 0 AF XY: 0.000213 AC XY: 29AN XY: 135896
GnomAD4 exome AF: 0.000106 AC: 154AN: 1458960Hom.: 2 Cov.: 29 AF XY: 0.000147 AC XY: 107AN XY: 726070
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.0000672 AC XY: 5AN XY: 74460
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 29, 2022 | The c.3494G>A (p.R1165Q) alteration is located in exon 35 (coding exon 34) of the FANCD2 gene. This alteration results from a G to A substitution at nucleotide position 3494, causing the arginine (R) at amino acid position 1165 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Fanconi anemia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 01, 2022 | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1165 of the FANCD2 protein (p.Arg1165Gln). This variant is present in population databases (rs549507714, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with FANCD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 526384). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Ovarian cancer Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University | Jan 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at